Potential Immunomodulatory Role of Specific Anticytomegalovirus Intravenous Immunoglobulin in Heart Recipients.

BACKGROUND: Specific anticytomegalovirus (anti-CMV) intravenous immunoglobulin (IVIG) has the potential to influence the immune response, but its complex mode of action has not been well evaluated. METHODS: An immunologic study of 6 CMV-seronegative heart transplant patients receiving anti-CMV prophylaxis with the use of ganciclovir and CMV-IVIG (150 mg/kg within 24 hours after transplantation and 100 mg/kg on days 2, 7, 14, 22, 35, 56, and 77 after transplantation) was performed in a single center. Lymphocyte subsets were evaluated by means of 4-color flow cytometry at the time of inclusion in the waiting list and at 3 months after transplantation. RESULTS: High-risk heart recipients receiving CMV-IVIG showed a clear reduction in the frequency of activated CD4+CD38+DR+ T-helper cells at 3 months after transplantation compared with a group of 27 untreated control subjects who received only anti-CMV prophylaxis with the use of ganciclovir. In this study, an increase of CD19+CD27-IgM+IgD+ naïve B cells was also observed in seronegative recipients after prophylaxis with the use of CMV-IVIG but not in control subjects. None of the CMV-IVIG-treated recipients developed acute cellular rejection during the 1st 6 months after transplantation. CONCLUSIONS: The immune modulation of activated CD4+ lymphocyte and of naïve B-cell subsets after CMV-IVIG use should be further evaluated in future prospective studies with higher numbers of patients.

Evaluation of an immunological score to assess the risk of severe infection in heart recipients.

BACKGROUND: We previously reported how specific humoral and cellular immunological markers that are readily available in clinical practice can be used to identify heart transplant recipients (HTR) at risk of developing severe infections. In this study, we perform an extended analysis to identify immunological profiles that could prove to be superior to individual markers in assessing the risk of infection early after heart transplantation. METHODS: In a prospective follow-up study, we evaluated 100 HTR at 1 week after transplantation. Laboratory tests included determination of immunoglobulin (Ig) levels (IgG, IgA, IgM), complement factors (C3 and C4), and lymphocyte subsets (CD3+, CD4+, CD8+ T cells, B cells, and natural killer [NK] cells). The prevalence of infection during the first 3 months was registered at scheduled visits after transplantation. Severe infections were defined as all infections requiring hospitalization and intravenous antimicrobial therapy. RESULTS: During follow-up, 33 patients (33%) developed severe infections. The individual risk factors of severe infection, according to the Cox regression analysis, were as follows: IgG <600 mg/dL (hazard ratio [HR], 2.41; 95% confidence interval [CI], 1.21-4.78; P = 0.012), C3 <80 mg/dL (HR, 4.65; 95% CI, 2.31-9.38; P < 0.0001), C4 <18 mg/dL (HR 2.30, 95% CI, 1.15-4.59; P = 0.018), NK count <30 cells/µL (HR 4.07, 95% CI, 1.76-9.38; P = 0.001), and CD4 count <350 cells/µL (HR, 3.04; 95% CI, 1.47-6.28; P = 0.0027). An immunological score was created. HRs were used to determine the number of points assigned to each of the 5 previously mentioned individual risk factors. The score was obtained from the sum of these factors. In the multivariate Cox regression analysis, the immunological score was useful for identifying patients at risk of infection and was the only variable that maintained a significant association with the development of infection, after adjustment for the 5 individual factors. CONCLUSION: Patients with an immunological score ≥13 were at the highest risk of severe infections (HR, 9.29; 95% CI, 4.57-18.90; P < 0.0001). This score remained significantly associated with the risk of severe infection after adjustment for clinical risk factors of infection. An immunological score was useful for identifying HTR at risk of developing severe infections. If this score is validated in multicenter studies, it could be easily introduced into clinical practice.

Kinetics of functionally distinct T-lymphocyte subsets in heart transplant recipients after induction therapy with anti-CD25 monoclonal antibodies.

T cells are involved in the maintenance of immunocompetence and in the development of alloimmune responses in solid organ transplant recipients. The kinetics of functionally distinct T-cell subsets in peripheral blood has received little attention in the field of heart transplantation. We performed a simultaneous analysis of the maturation, activation, and regulatory profiles of T cells using 4-color flow cytometry in a study of 77 heart recipients. Induction therapy included 2 doses of anti-CD25 monoclonal antibodies (daclizumab). Lymphocyte subsets were prospectively evaluated at different times before and up to 1 year after transplantation in 46 heart recipients. A separate cross-sectional study was performed in 33 heart recipients who had received a transplant more than 1 year previously to evaluate abnormalities persisting in the long term. As compared with baseline values, a decrease in regulatory CD4+ T-cell percentages (CD4+CD127lowCD25highFoxP3+) was observed from day 7 to 12 months after transplantation. Interestingly, T cells expressing the beta chain of IL-2 (CD122+) remained stable during the first 3 months. A significant decrease in the activation status of CD4 T cells was documented from day 7 to 1 year after transplantation, while the activation status of CD8+ T cells remained stable during follow-up. Compared with values for healthy controls (n=36), higher CD8+ terminally differentiated effector memory percentages (CD8+CD45RA+CCR7-) were observed from baseline up to more than 1 year after transplantation. Rejection was associated with higher levels of these cells during the first 6 months after transplant. We characterized the abnormalities in distinct functional T-cell subsets at different times before and after heart transplantation. Some of these abnormalities should be further investigated as biomarkers of clinical complications.

Evaluation of lymphoproliferative responses by carboxy fluorescein succinimidyl ester assay in heart recipients with infections.

The analysis of proliferative responses using 5,6-carboxyfluorescein diacetate succinimidyl ester (CFSE) in flow cytometry is widely used to assess lymphocyte function. The aim of this study was to evaluate nonspecific and specific lymphoproliferative responses using CFSE in heart recipients before and after transplantation and their association with the development of infection. We used four-color flow cytometry to measure the response of peripheral CD3+, CD4+, and CD8+ T cells to phytohemagglutinin mitogen (PHA), tetanus toxoid, hepatitis B, and influenza vaccines using a CFSE proliferation assay in 12 heart recipients and 8 healthy control subjects. Recipients were prospectively evaluated. Immunological studies were performed before and at 3 months after transplantation. A 12-month clinical follow-up examination sought to detect the prevalence of severe infectious complications. Heart recipients (infected [n = 7] and uninfected [n = 5]) disclosed significantly lower percentages of proliferative responses than healthy controls against PHA at both study points. Baseline CD3+, CD4+, and CD8+, antitetanus proliferative responses were significantly lower in infected heart recipients than controls. Patients who developed infections displayed significantly lower percentages of CD3+CFSE and CD8+CFSE cells to PHA mitogen at 3 months after transplantation versus those without infections. In conclusion, nonspecific T-cell reactivity to PHA was lower in heart recipients with posttransplantation infections.

Decreased levels of serum complement C3 and natural killer cells add to the predictive value of total immunoglobulin G for severe infection in heart transplant recipients.

BACKGROUND: Infection remains a source of mortality in heart recipients. We previously reported that post-transplant immunoglobulin G (IgG) quantification can help identify the risk for infection. We assessed whether other standardized parameters of humoral and cellular immunity could prove useful when identifying patients at risk of infection. METHODS: We prospectively studied 133 heart recipients over a 12-month period. Forty-eight patients had at least one episode of severe infection. An event was defined as an infection requiring intravenous antimicrobial therapy. RESULTS: Cox regression analysis revealed an association between the risk of developing infection and the following: lower IgG2 subclass levels (day 7: relative hazard [RH] 1.71; day 30: RH 1.76), lower IgA levels (day 7: RH 1.61; day 30: RH 1.91), lower complement C3 values (day 7: RH 1.25), lower CD3 absolute counts (day 30: RH 1.10), lower absolute natural killer [NK] cell count (day 7: RH 1.24), and lower IgG concentrations (day 7: RH 1.31; day 30: RH 1.36). Cox regression bivariate analysis revealed that lower day 7 C3 levels, IgG2 concentration, and absolute NK cell count remained significant after adjustment for total IgG levels. CONCLUSIONS: Data suggest that early immune monitoring including C3, IgG2, and NK cell testing in addition to IgG concentrations is useful when attempting to identify the risk of infection in heart transplant recipients.

Restoration of humoral immunity after intravenous immunoglobulin replacement therapy in heart recipients with post-transplant antibody deficiency and severe infections.

IgG hypogammaglobulinemia is a risk factor for infection in heart recipients. We assessed reconstitution of humoral immunity after non-specific intravenous immunoglobulin (IVIg) replacement therapy administered to treat secondary IgG hypogammaglobulinemia in heart recipients with severe infections. The study population comprised 55 heart recipients who were administered IVIg (IVIg group) and 55 heart recipients with no severe infectious complications (control group). An event was defined as a severe infection requiring intravenous drug therapy during the first year after transplantation. The IVIg protocol comprised non-specific 5% pasteurized IVIg at a dose of 300-400 mg/kg/months. IgG titers were lower in the IVIg group than in controls at seven d (577 vs. 778 mg/dL, p < 0.001) and at one month (553 vs. 684, p = 0.003). After IVIg therapy, IgG concentrations were similar in both groups at three months (681 vs. 737, p = 0.25) and at six months (736 vs. 769, p = 0.46). At three months, the IVIg group had higher levels of antitetanus toxoid and anti-HBs (ELISA, 2.07 ± 2.11 vs. 0.60 ± 1.24 mg/dL [p = 0.003] and 42 ± 40 vs. 11 ± 31 IU/mL [p = 0.005], respectively) than controls. The mean number of infectious complications was significantly lower after IVIG therapy in the IVIG group. IVIg was associated with restoration of humoral immunity in heart recipients with post-transplant IgG hypogammaglobulinemia and severe infections.

Steroid use in heart transplant patients in Spain in the current era: a multicenter survey.

OBJECTIVE: Steroid withdrawal (SW) from maintenance therapy in heart transplant patients is still a controversial subject. We designed a questionnaire to ascertain the attitudes and procedures of a number of Spanish heart transplant units (16) regarding the use/withdrawal of steroids as part of the immunosuppressive maintenance therapy. MATERIALS AND METHODS: We sent an 11-item questionnaire to the clinical director in charge of each unit. The questionnaire was completed and returned by 14 units. RESULTS: In 21.5% of the centers SW was performed in all patients, while 78.5% of the centers only performed SW in selected patients. In 57% of units SW was performed at 12 months posttransplantation and between 6 and 12 months in the rest. Fewer than 20% of patients were steroid-free in 46% of units while in 23% of units this proportion was >50%. In 11 units, the minimum prednisone dose administered was

The potential role of T-cell memory distribution as predisposing factor for rejection in heart transplant recipients.

CD4 T cells play a significant role in the pathogenesis of rejection, providing help to alloreactive CD8 and B cells, however, the exact contribution of each memory compartment in vivo has not been defined. They are also important for the maintenance of tolerance due to regulatory activity of specialized subsets. In this study, we assessed changes in frequencies of functionally distinct lymphocyte subsets of peripheral blood (PBLs) in 26 heart transplant recipients (HT) in association with rejection episodes. Patients who developed rejection (n = 7), namely Grade 3B (n = 1), 3A (n = 4), or 2 (n = 2), in comparison with those with stable graft function displayed at baseline (pre-HT) higher percentages of naive (CCR7+CD45RA+) CD4 T cells (median 48 vs 36.6%; P = .035) and lower percentages of central memory (CCR7+CD45RA-) CD4 T cells (33.3 vs 46.5%; P = .035). At 30 days post-HT, CD4/CD127(low)FoxP3+ T cells were significantly reduced among patients with rejection episodes (0.84 vs 2.15%; P = .042). CD8 final effector T cells were increased at 90 days post-HT among those patients who experienced rejection (TEM2: 60.8 vs 31.9%; P < .1), at the expense of shrinking CD8 central memory compartment (TCM: 8.6 vs 12.9%; P = .046). The potential role of T-cell memory distribution should be further evaluated in HT patients as possible markers to discriminate patients at risk for rejection.

Malignancy after heart transplantation: incidence, prognosis and risk factors.

The Spanish Post-Heart-Transplant Tumour Registry comprises data on neoplasia following heart transplantation (HT) for all Spanish HT patients (1984-2003). This retrospective analysis of 3393 patients investigated the incidence and prognosis of neoplasia, and the influence of antiviral prophylaxis. About 50% of post-HT neoplasias were cutaneous, and 10% lymphomas. The cumulative incidence of skin cancers and other nonlymphoma cancers increased with age at HT and with time post-HT (from respectively 5.2 and 8.9 per 1000 person-years in the first year to 14.8 and 12.6 after 10 years), and was greater among men than women. None of these trends held for lymphomas. Induction therapy other than with IL2R-blockers generally increased the risk of neoplasia except when acyclovir was administered prophylactically during the first 3 months post-HT; prophylactic acyclovir halved the risk of lymphoma, regardless of other therapies. Institution of MMF during the first 3 months post-HT reduced the incidence of skin cancer independently of the effects of sex, age group, pre-HT smoking, use of tacrolimus in the first 3 months, induction treatment and antiviral treatment. Five-year survival rates after first tumor diagnosis were 74% for skin cancer, 20% for lymphoma and 32% for other tumors.

The potential impact of substitutive therapy with intravenous immunoglobulin on the outcome of heart transplant recipients with infections.

Hypogammaglobulinemia has been proposed to be a risk factor for infection after heart transplantation (OHT). Infection is a leading cause of morbility and mortality among these patients. In a retrospective study we analyzed the impact of substitutive therapy with nonspecific intravenous immunoglobulin (IVIG) on the outcomes of heart transplant patients with infections. We analyzed the outcome of 123 consecutive heart transplant recipients in our center from June 1996 to November 2005. Their mean age was 53 years (range = 22 to 69 years), and the mean follow-up = 51 months, (range = 1 to 124 months). Twenty-nine patients with hypogammaglobulinemia (mean serum immunoglobulin G levels = 480 mg/dL) experienced severe infections due to cytomegalovirus (CMV) disease, n = 4; CMV disease + another infection, n = 6; CMV infection, n = 4; CMV infection + other infection, n = 3; pulmonary nocardiosis, n = 2; recurrent pneumonia, n = 2; clostridium-difficile-associated diarrhea, n = 2; pulmonary tuberculosis, n = 1; bacterial infections, n = 5. They were treated with IVIG (400 mg/kg every 21 days) with the goal to reach normal serum immunoglobulin G levels (>700 mg/dL). Overall (n = 123), a logistic regression analysis showed IVIG therapy to be associated with a decreased risk of death [odds ratio (OR) = 0.204, 95% confidence interval (CI) = 0.04 to 0.92, P = .03]. Among patients who developed infections during follow-up (n = 70), IVIG therapy was also associated with a lower risk of death (OR = 0.104, CI = 0.02 to 0.50, P = .0047). When we stratified patients with CMV disease (n = 24) according to the presence (n = 10) or absence (n = 14) of IVIG therapy, the mortality rate of IVIG-treated patients was 20% versus 71% for non-IVIG treated patients [OR = 0.06, CI = 0.0060 to 0.63, P = .01]. The use of nonspecific IVIG in OHT with hypogammaglobulinemia and infections might reduce the risk of death. Randomized studies in a larger cohort of patients are necessary to confirm these results.

Gastrointestinal complications in heart transplant patients: MITOS study.

INTRODUCTION: The most frequent immunosuppressive treatment complications in solid organ transplant recipients are gastrointestinal (GI) disorders. MATERIALS AND METHODS: An observational, cross-sectional study to evaluate the prevalence and management of GI complications in transplanted patients was conducted via a written questionnaire given to doctors at their practice. RESULTS: This study included 1788 patients; 181 corresponded to heart transplant recipients. The mean age for the heart transplant patients was 58.7 +/- 11.8 years. The mean time from the transplantation was 5.2 +/- 4.4 years. GI complications were seen in 38.7% of cases. Regarding the clinical management, in 72.9% of cases patients with GI complications received pharmacologic treatment, 86.3% with gastric protectors, 32.8% reduced the dose of some drug, 8.1% interrupted the drug temporarily, and 10.9% discontinued the drug permanently. The drug that was always discontinued was mycophenolate mofetil (MMF), and in 85.7% of cases in which the dose of an immunosuppressive drug was reduced, the reduced drug was also MMF. CONCLUSIONS: Almost 40% of heart transplant recipients suffered GI complications which affected daily activities in most cases. The most used strategy to manage these complications was based on a treatment with gastric protectors together with dose reduction and/or partial or definitive MMF discontinuation.

Impaired anti-pneumococcal polysaccharide antibody production and invasive pneumococcal infection following heart transplantation.

An increased risk of invasive pneumococcal infection has been described among adult heart transplant (HT) recipients. Vaccination has been recommended before HT but the appropriate time for revaccination is not known. In a preliminary analysis of a prospective study involving a cohort of 32 HT recipients receiving daclizumab and triple immunosuppresion therapy, a progressive decline in pneumococcal polysaccharide antibody (anti-PPS) levels was observed during the first year after HT. One of the patients who was found to have a decrease in the levels of anti-PPS developed severe pneumococcal meningitis 20 months after HT. Before HT he had received non-conjugated 23-valent pneumococcal vaccine and showed a normal post-immunization anti-PPS production. The data suggest that long-term immunologic monitoring might be useful to recognize impairment of antibody responses under immunosuppressive therapy in HT.

IgG monitoring to identify the risk for development of infection in heart transplant recipients.

Infectious complication represents a significant source of morbidity and mortality in heart transplant recipients. To assess humoral immunity markers that can predict the development of infection, 38 consecutive recipients of heart transplants performed at a single center were prospectively studied. Induction therapy included daclizumab. Immunoglobulin (IgG, IgA, IgM) and complement factors (C3, C4, and factor B) were performed by nephelometry in peripheral blood samples obtained before transplantation, and 7 days and 1 month after transplantation. During a mean follow-up of 16.9 months, 13 patients had at least one episode of infection (34.2%). Eight of these were cytomegalovirus (CMV) infections treated with intravenous ganciclovir, 2 were bacterial pneumonia, 1 patient had bacterial septicemia, 1 patient had urinary tract infection, and 1 patient had pulmonary nocardiosis. No significant association was found between infection and age, sex, immunosuppression, CMV serostatus of donor and recipient, or treated rejection episodes. Pre-transplant IgG (below median value=1140 mg/dL; relative risk [RR] 3.69; 95% confidence interval [CI] 1.01-13.54; P=0.04) and post-transplant IgG levels at day 7 (below median value=679 mg/dL; RR 11.21; CI 1.04-89.48; P=0.022) were associated with an increase in the risk for developing infections. Early monitoring of immunoglobulin levels might help to identify the risk for developing infection in heart transplantation.

Decreased levels of serum immunoglobulins as a risk factor for infection after heart transplantation.

OBJECTIVE: We aimed to assess humoral immunity markers that provide prognostic value for the development of infections in heart transplant recipients. PATIENTS AND METHODS: Forty-one heart transplant recipients underwent humoral immunity studies, including Immunoglobulin (IgG, IgA, IgM) and IgG subclasses determined by nephelometry on serum samples obtained before transplantation and 1 month after transplantation. Potential clinical risk factors were evaluated: waiting time for transplantation, pretransplant cytomegalovirus (CMV) serologic status of donor and recipient; recipient age; gender; cardiac disease severity before transplantation; type of immunosuppression; and occurrence of rejection. OUTCOME MEASURES: We measured infections requiring intravenous (IV) drug therapy during the first year. The association between variables and outcome was assessed using Cox proportional hazards modelling. Immunoglobulin levels were split into two groups using the median value observed as the cut-off. RESULTS: Of 41 patients studied, 19 (46%) had at least one episode of infection, 16 of which were CMV infections treated with IV gancyclovir, 1 CMV disease + aspergillosis and 2 bacterial pneumonia. Pretransplant IgG (<1055 mg/dL; RR 5.32; 95% confidence interval [CI] 1.73 to 16.29; P = .0034); pretransplant IgG1 (<695 mg/dL; RR 4.80; CI 1.57 to 14.68; P = .006), and posttransplant IgG levels (<589 mg/dL; RR 3.38; CI 1.21 to 9.44, P = .019) were associated with an increased risk of developing infections. Both waiting time for transplantation (RR 0.95; CI 0.91 to 0.98, P = .007) and pretransplant cardiac disease severity (RR 1.94; CI 1.17 to 3.21, P = .009) were significant risk factors for infection. After adjustment for clinical predictive variables, decreased values of posttransplant IgG remained significant predictors. CONCLUSIONS: The existence of decreased levels of IgG in the setting of heart transplantation was associated with an higher risk for infection. Monitoring of immunoglobulin levels, a rapid and well-standardized nephelometric determination, in heart transplantation, may identify a subset of patients at risk for development of infections.

Hypogammaglobulinemia after heart transplantation: use of intravenous immunoglobulin replacement therapy in relapsing CMV disease.

Secondary hypogammaglobulinemia after heart transplantation may follow immunosuppressive therapy with the resultant increased risk of infections, including cytomegalovirus (CMV) disease. There is limited information on the use of intravenous immunoglobulin replacement therapy (IVIG) in heart-transplanted patients with hypogammaglobulinemia and CMV disease. We present data on five consecutive heart-transplanted patients with relapsing CMV disease, four of whom developed gastrointestinal disease. The immunosuppressive regimen included prednisone, cyclosporine A, azathioprine, mycophenolate mofetil, tacrolimus and antithymocyte globulin (ATG). Evaluation revealed CMV antigenemia. All the patients had been treated with intravenous ganciclovir. In addition, hyperimmune CMV immunoglobulin was administered in three patients. Significantly reduced levels of immunoglobulin G (IgG) were observed in the patients as compared with 15 heart-transplanted individuals without CMV disease [mean IgG levels: 323+/-18 and 639+/-63 mg/dl, respectively (p=0.003)]. IVIG [FLEBOGAMMA], 200-400 mg/kg every 21 days with the goal of maintaining normal serum IgG levels, was added for the treatment of CMV disease. Selected batches with the highest anti-CMV titers were set apart for the treatment of the patients. IVIG treatment, in combination with antiviral therapy, proved able to control CMV disease. There was a favorable clinical response and the patients became free of gastrointestinal symptoms. Detection of CMV antigens was negative after treatment. During IVIG therapy no immediate or delayed adverse effects were observed. Even if our survey was limited to five cases, the results suggest that addition of IVIG to antiviral chemotherapy might improve outcome in heart-transplanted patients with hypogammaglobulinemia and CMV disease.

Results of percutaneous revascularization in cardiac allograft vascular disease.

OBJECTIVES: To evaluate the outcome of transplant patients with CGD treated by PTCA in our center. METHODS: We retrospectively analyzed the medical records of all PTCA procedures performed on heart transplant patients in our hospital. RESULTS: Among 13 patients (11 men, 52.9+/-9.7 years), 20 lesions were treated with PTCA with 95% initial angiographic success. The indications for PTCA was heart failure or ventricular systolic dysfunction (n=4), of ischemia (n=4) and angiographic criteria alone (n=5). Ten lesions were treated with balloon angioplasty. A stent was implanted in 10 lesions, including one patient with a previous atherectomy. There were no complications. Angiographic follow-up was performed on 11 patients, four of whom (36%) showed restenosis. Mean follow-up was 33 months. Four patients (30.8%) are alive without retransplantation, two (15.4%) are alive after retransplantation, and seven (53.4%) died, all from cardiac causes. Graft survival rates estimated by the Kaplan-Meier method were 62% in the first year and 46% in the second year. CONCLUSIONS: Our results suggest that PTCA represents a palliative method of treatment for heart transplant patients with CGD.

[The syndrome of mid-ventricular obstruction with apical aneurysm in hypertrophic myocardiopathy: presentation of a case]. / El "síndrome" de obstrucción medioventricular con aneurisma apical en la miocardiopatía hipertrófica: presentación de un caso.

We report an 81-year-old woman with hypertrophic cardiomyopathy, midventricular obstruction and associated apical aneurysm partially dyskinetic. At admission she showed a lateral acute myocardial infarction with sustained episodes of uniform ventricular tachycardia and subtle cardiac physical findings. Old apical infarction was suggested by resting thallium defects in the absence of obstructive coronary disease. The ECG revealed persistent ST elevation in the anteroapical leads without Q waves at discharge. This case report represents a rare example, in a previously asymptomatic elderly woman, of a distinct syndrome within the wide clinical spectrum of hypertrophic cardiomyopathy.

[Cardiac pathology of extracardiac origin (II). The cardiac repercussion of amyloidosis and hemochromatosis]. / Patología del corazón de origen extracardíaco (II). Repercusión cardíaca de la amiloidosis y de la hemocromatosis.

Although rare, amyloidosis and hemochromatosis are the infiltrative diseases in which the heart is more frequently involved. The most common clinical presentation is heart failure with hemodynamic features of restrictive heart disease in cardiac amyloidosis. The diagnosis is often made because of symptoms of other organ involvement, although sometimes cardiac symptoms may be the initial manifestation. The non-specific clinical presentation and the low prevalence of these cardiomyopathies make the diagnosis difficult if the clinician does not suspect it. Once symptoms develop, the evolution is fast. Usually, the unsatisfactory and ineffective treatment of amyloidosis and hemochromatosis contribute to the poor prognosis. The indication of cardiac transplantation in advanced cases is questionable because of the high recurrence of the illness.